Macrophage migration inhibitory factor is necessary for the lipo-oligosaccharide-induced response by modulation of Toll-like receptor 4 in monocytes from GBS patients

J Neuroimmunol. 2013 Apr 15;257(1-2):67-75. doi: 10.1016/j.jneuroim.2013.01.006. Epub 2013 Feb 12.

Abstract

Previous studies have suggested that macrophage migration inhibitory factor (MIF) may play a critical role in the pathogenesis of Guillain-Barre syndrome (GBS); however, its definite mechanism remains unknown. In this study, we prepared the monocytes from the peripheral blood mononuclear cells (PBMCs) of GBS patients and the controls. Lipo-oligosaccharide (LOS) from Campylobacter jejuni was used as the stimulus of the monocytes in vitro and siRNA-MIF was used to explore the roles of MIF in LOS-induced response. Significantly, silencing of MIF attenuated the LOS-induced up-regulation of Toll-like receptor 4 (TLR4) and translocation of NF-кB into the nucleus; we also observed the up-regulation of IL-12p40, TNF-α, IL-6, CXCL8 and CCL5 in GBS monocytes with LOS stimulus; and siRNA-MIF overrided the effects of LOS on the production of the TNF-α, IL-6, and CXCL8. Conclusively, our study provides evidences that MIF may participate in the pathogenesis of GBS by modulating the LOS-induced response through TLR4 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Female
  • Guillain-Barre Syndrome / etiology
  • Guillain-Barre Syndrome / immunology*
  • Guillain-Barre Syndrome / pathology
  • Humans
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / physiology*
  • Lipopolysaccharides / physiology*
  • Macrophage Migration-Inhibitory Factors / antagonists & inhibitors
  • Macrophage Migration-Inhibitory Factors / physiology*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Toll-Like Receptor 4 / physiology*
  • Young Adult

Substances

  • Lipopolysaccharides
  • Macrophage Migration-Inhibitory Factors
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • lipid-linked oligosaccharides
  • Intramolecular Oxidoreductases
  • MIF protein, human